An overview of oscillatory fluid flow as a potent loading-induced physical signal in bone cells

摘要

Recently, loading induced fluid flow through the lacunar/canalicular system has been shown to be a potent physical signal in the regulation of bone cell metabolism. However, to date most investigators studying the effect of fluid flow on bone cells in vitro have applied steady or pulsatile flow profiles rather than the reversing oscillatory flow profile that occurs in vivo due to mechanical loading. This presentation represents an overview of our group's research findings aimed at determining the effect of oscillatory flow profiles on bone cell metabolism and biochemical signalling pathways. It also highlights some apparent differences between the response of bone cells to oscillatory flow relative to chronic or steady flow. We have focused on three biological response or outcome variables that occur on a variety of time scales. In terms of very early signalling mechanisms we examined the role of intracellular calcium (Ca{sup}2+ ) mobilization which occurs on the order of minutes after stimulation. In terms of intermediate time frame responses, we have considered both PGE2 release, MAP kinase activity, and TNF-α stimulated NFκB activity, all of which occur over a period of hours. Finally, we considered mRNA levels of the gene for osteopontin (the most abundant non-collagenous extracellular matrix protein in bone) which occurs between 24 and 72 hours after stimulation.